Ethylene oxide sterilization process indicator inks

ABSTRACT

Water-based chemical indicator inks for ethylene oxide sterilization processes and methods for its use. The chemical indicator ink contains at least one pH indicator dye selected from the group consisting of Bromocresol green, Bromophenol blue, Methyl red, Ethyl orange, and combinations thereof. The pH indicator dye undergoes an irreversible color change when exposed to ethylene oxide vapor in the presence of low-temperature steam, but when exposed to other sterilization processes either does not undergo a color change or undergoes a color change that is different than is obtained when exposed to ethylene oxide.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a divisional of U.S. application Ser. No. 10/178,192, filed Jun.24, 2002, now U.S. Pat. No. 6,800,124.

BACKGROUND OF THE INVENTION

The present invention relates to ethylene oxide sterilization processindicators and, more particularly, to chemical indicator inks that aredesigned to undergo an irreversible color change when exposed toethylene oxide vapor in the presence of low-temperature steam, and tomethods for indicating that an article has undergone ethylene oxidesterilization processing.

Biological and medical operations such as hospitals, medicallaboratories and other allied health facilities, which often come incontact with microorganisms and other microbiological agents, employ avariety of technology to control both infection and contamination. Whilecompositions such as germicides, antiseptics and bacteriostats areeffective in controlling widespread growth of biological contaminants,they do not go as far as to completely eliminate these agents.

Since many of the materials and instruments that are used in modernhospitals must be kept sterile, but cannot withstand the heat and/ormoisture encountered in a conventional steam sterilization process,there is a growing trend towards the use of an alkylating agent as thesterilization agent. The most popular sterilization alkylating agentpresently employed is ethylene oxide gas, generally in an admixture withan inert gaseous diluant such as carbon dioxide, nitrogen,tricloromonofluoromethane, dichlorodifluoromethane, and the like.Ethylene oxide gas can be used as a sporicidal and virucidal agent.Consequently, ethylene oxide sterilization processes are often employedto ensure total eradication of microorganisms.

Since ethylene oxide gas readily diffuses through all of the commonlyemployed packaging materials and is highly effective in killingmicroorganisms at temperatures well below those required for heatsterilization techniques, it enables efficient sterilization of manyitems, particularly those made of thermoplastic materials, which cannotwithstand heat sterilization. The process generally involves placing anitem in a chamber and subjecting it to ethylene oxide vapor. When usedproperly, ethylene oxide is not only lethal to all known microorganismsat ordinary temperature, but it is also non-corrosive, readily removedby aeration, easily handled and stored, and has a low toxicity tohumans.

Known in the art are methods for indicating that an article hasundergone ethylene oxide sterilization. For example, U.S. Pat. Nos.2,998,306 and 3,098,751 teach methods employing water-based andsolvent-based chemical indicators, respectively, which undergo anirreversible color change when placed in an ethylene oxide environment.However, the number of color changes available from these indicators islimited. Moreover, the organic solvents employed in some of thesechemical indicators present an environmental hazard. Thus, there is aneed for chemical indicator inks that exhibit additional color changesupon exposure to ethylene oxide vapor in the presence of low-temperaturesteam and do not contain high concentrations of volatile organiccompounds.

SUMMARY OF THE INVENTION

The present invention meets this need by providing water-based chemicalindicator inks that contain at least one pH indicator dye. The inks areeffective in showing whether or not treated materials have beensubjected to sterilizing conditions using ethylene oxide as thesterilization medium.

In accordance with one aspect of the present invention, a water-basedchemical indicator ink for ethylene oxide sterilization processes isprovided containing at least one pH indicator dye selected from thegroup consisting of Bromocresol green, Bromophenol blue, Methyl red,Ethyl orange, and combinations thereof. The pH indicator dye undergoesan irreversible color change when exposed to ethylene oxide vapor in thepresence of low-temperature steam. The low-temperature steam has atemperature of less than about 145° F. Moreover, the pH indicator dyewhen exposed to other sterilization processes such as formaldehyde gas,high-temperature steam, dry heat, or combinations thereof, either doesnot undergo a color change or undergoes a color change that is differentthan is obtained when exposed to ethylene oxide vapor.

The water-based chemical indicator ink can comprise a solution includingthe pH indicator dye dissolved in water. The water-based chemicalindicator ink can further contain a powdered and crystallizedhexahydrate metal salt. In addition, the water-based chemical indicatorink can further contain an acidic compound such as citric acid, at leastone thickening agent, a white pigment such as titanium dioxide, abinder, and/or a foam suppressor such as an aliphatic polyol blend. Theacidic compound retards a color change of the water-based chemicalindicator ink. The thickening agent can be selected from the groupconsisting of hydrous aluminum silicates, hydrous magnesium silicates,and combinations thereof. The binder can be a polymeric materialselected from the group consisting of polyvinyl alcohol, methylcellulose, and combinations thereof.

In accordance with another aspect of the present invention, a method isprovided for indicating that an article has undergone ethylene oxidesterilization processing. The method comprises providing a water-basedchemical indicator ink containing at least one pH indicator dye selectedfrom the group consisting of Bromocresol green, Bromophenol blue, Methylred, Ethyl orange, and combinations thereof. The pH indicator dyeundergoes an irreversible color change when exposed to ethylene oxidevapor in the presence of low-temperature steam. The method furthercomprises applying the water-based chemical indicator ink to an article,subjecting the article to a concentration of ethylene oxide vapor in thepresence of low-temperature steam, and observing the chemical indicatorink for a color change that is visually indicative of whether theconcentration of ethylene oxide vapor has been applied for a timesufficient to sterilize the article.

The method can further comprise measuring the integrated effect ofsubjecting the article to the concentration of ethylene oxide vapor inthe presence of low-temperature steam for the time sufficient tosterilize the article. In addition, the method can comprise applying thewater-based chemical indicator ink to a substrate to form an ethyleneoxide sterilization process indicator prior to applying the ink to thearticle. The step of applying the water-based chemical indicator ink toa substrate can be accomplished by printing the ink on the substrate inthe shape of squares or insignia to form the indicator. In addition, theindicator can be secured to a package containing the article andsubjected to the concentration of ethylene oxide vapor in the presenceof low-temperature steam.

Accordingly, it is a feature of the present invention to provide awater-based chemical indicator ink for printing insignia on a substratethat is visually indicative of whether a concentration of ethylene oxidehas been applied for a time sufficient to ensure sterilization within atreating chamber or within the contents of a package subjected toethylene oxide gas treatment therein. It is also a feature of thepresent invention to provide a printed informative device for ethyleneoxide sterilization, which is cost effective, relatively simple to use,resists contaminating the goods being sterilized, and is environmentallyfriendly. This and other features and advantages of the presentinvention will become apparent from the following detailed descriptionand the appended claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides water-based chemical indicator inks forethylene oxide sterilization processes. The water-based chemicalindicator ink contains at least one pH indicator dye. The pH indicatordye will undergo a visual, distinct and irreversible color change whenexposed to ethylene oxide vapor in the presence of low-temperaturesteam. Accordingly, the water-based chemical indicator ink compositionof the present invention can be applied to a substrate to form anethylene oxide sterilization process indicator that is effective insignaling whether an article has been subjected to ethylene oxidesterilization processing.

Unlike biological indicators which utilize dried microbes and can becultured in sterile media following processing to ensure sterilization,the water-based chemical indicator ink of the present invention merelyshows that an article has undergone ethylene oxide sterilizationprocessing. It does not indicate whether any microbial contaminants wereeffectively destroyed. Consequently, it is important for the operator ofthe ethylene oxide sterilization process to follow correct sterilizationprotocols.

As discussed in U.S. Pat. No. 3,098,751, the efficacy of sterilizationby ethylene oxide depends upon a number of factors, the most importantof which are the concentration of the ethylene oxide in thesterilization vessel or chamber, the moisture present, the time ofcontact with the ethylene oxide, and the temperature of the treatment.Since one of the principal advantages of ethylene oxide sterilization isthat it is effective at relatively low temperature, most sterilizers areoperated at ambient temperature up to about 145° F. (which falls withinthe definition of “low-temperature” as used herein). Humidity in therange from 40 to 60% relative humidity (which falls within thedefinition of “steam” as used herein) has been found to be mosteffective, and in practice this range can be maintained. The effects oftime and concentration are inter-related and generally expressed as thelower the concentration, the longer time of exposure required to effectsterilization.

The telltales of the present invention, as well as the inventiondescribed in U.S. Pat. No. 3,098,751, measure the integrated effect oftime of exposure, and the concentration of the ethylene oxide, in thepresence of water vapor (i.e., “steam”). The telltales depend upon thechemical reaction of ethylene oxide on magnesium chloride, crystallizedwith water,MgCl₂.6H₂Oby which magnesium hydroxide and epichlorohydrin are produced.MgCl₂.6H₂O+2(CH₂)O+pH indicator (color A)Mg(OH)₂+2CH₂O.H.CH₂Cl+pH indicator (color B)

When a known amount of acid is initially added to the composition, aknown minimum amount of ethylene oxide will have been absorbed andreacted with the acid when the mass becomes alkaline, after exposure tomoist ethylene oxide. This alkalinity is visually observed when a pHindicator dye in the composition changes from one color when acidic (A)to another color when the composition is alkaline (B).

These reactions can be utilized when the composition is in the form of adried printing ink, which is applied by the process of printing,particularly by flexographic printing of squares or insignia on asubstrate. The freshly applied squares or insignia are allowed to dry,after which the printed indicators are used as telltales to indicatethat moist ethylene oxide has been present in sufficient concentrationfor a long enough time to effectively sterilize the goods or articlescontained in the sterilizing vessel or chamber.

The indicator ink consists of a thickened liquid ink base, powderedmagnesium chloride with water of crystallization (MgCl₂.6H₂O), and a pHindicator dye. However, unlike the flexographic ink of U.S. Pat. No.3,098,751, the chemical indicator ink of the instant invention, whichdries rapidly by evaporation, is water-based. The water-based chemicalindicator ink consists generally of:

1) a polymer dissolved in water,

2) a pH indicator dye,

3) a thickener,

4) an acidic compound, and

5) a defoamer.

The present invention provides color changes not contemplated by theprior art. Acidic material used reacts with alkali liberated whenethylene oxide reacts with magnesium chloride. A white pigment is alsoused with the pH indicator dye to enhance the color change.

In accordance with one embodiment of the present invention, the pHindicator dye can be Bromocresol green (cas. #76-60-8) or3′,3″,5′,5″-tetrabromo-m-cresol sulfonephthalein. The chemical structurefor this pH indicator dye is:

In accordance with another embodiment of the present invention, the pHindicator dye can be Bromophenol blue (cas. #115-39-9) or 3′,3″,5′,5″-tetrabromophenol-sulfonephthalein. The chemical structure for this pHindicator dye is:

In accordance with another embodiment of the present invention, the pHindicator dye can be Ethyl orange sodium salt (cas. #62758-12-7) or[4-(4-diethylaminophenylazo)benzenesulfonic acid, sodium salt]. Thechemical structure for this pH indicator dye is:

In accordance with another embodiment of the present invention, the pHindicator dye can be Methyl red sodium salt (cas. #845-10-3) or{2-[4-(dimethylamino)phenylazo]benzoic acid} sodium salt. The chemicalstructure for this pH indicator dye is:

Each of the above-mentioned pH indicator dyes, when subjected toethylene oxide, exhibit a distinct and irreversible color change. Thecolor changes are visually very marked. Consequently, it is readilyapparent when viewing the ethylene oxide sterilization process indicatorof the present invention whether the materials associated therewith havebeen subjected to ethylene oxide sterilization processing. Individual pHindicator dyes, each exhibiting a distinct color change, can be combinedto form a single chemical indicator ink that exhibits its own distinctcolor change. The colors of the individual and combined pH indicatordyes of the present invention both before and after exposure to ethyleneoxide (ETO) vapor are set forth in Table 1 below.

TABLE 1 pH Indicator Dye(s) Before and After Exposure to ETO Vapor ColorBefore Color After No. pH Indicator Dye(s) Exposure to ETO Exposure toETO 1 Bromocresol green + Brick red Blue Methyl red 2 Bromophenol blue +Orange Blue Ethyl orange 3 Ethyl orange Pink Orange 4 Bromophenol blueYellow Blue 5 Bromophenol blue + Brick red Purple Methyl red 6Bromocresol green Orange Green

The water-based chemical indicator ink of the present invention can bean aqueous ink solution, wherein the pH indicator dye is dissolved inwater. The water-based chemical indicator ink can further include apowdered and crystallized hexahydrate metal salt that provides water soas to facilitate the sterilization reaction, and/or an acidic compound,i.e., citric acid, which acts as a color retarder ingredient. Further,the water-based chemical indicator ink can include a thickening agentsuch as talc (hydrous silicates of magnesium or aluminum). A whitepigment such as titanium dioxide can be added to the water-basedchemical indicator ink as a brightener for the pH indicator dye.Polyvinyl alcohol, methyl cellulose, and/or other polymeric materialscan also be added to assist in binding and stabilizing the water-basedchemical indicator ink until use. Moreover, the water-based chemicalindicator ink can further include a foam suppressor such as an aliphaticpolyol blend.

In accordance with another aspect of the present invention, a method isprovided for indicating that an article has undergone ethylene oxidesterilization processing, which comprises providing a water-basedchemical indicator ink as described herein, applying the ink to anarticle, subjecting the article to a concentration of ethylene oxidevapor in the presence of low-temperature steam, and observing the inkfor a color change that is visually indicative of whether theconcentration of ethylene oxide vapor has been applied for a timesufficient to sterilize the article. The method can further comprisemeasuring the integrated effect of subjecting the article to theconcentration of ethylene oxide vapor in the presence of low-temperaturesteam for the time sufficient to sterilize the article. In addition, themethod can comprise applying the ink to a substrate to form an ethyleneoxide sterilization process indicator prior to applying it to thearticle, or printing the ink on the substrate in the shape of squares orinsignia. Moreover, the method can comprise securing the ethylene oxidesterilization process indicator to a package containing an article andsubjecting the package to ethylene oxide sterilization.

In order that the invention may be more readily understood, reference ismade to the following example, which is intended to illustrate theinvention, but not limit the scope thereof.

The chemical indicator inks used in the example that follows wereprepared with the ingredients listed in Table 2 below.

TABLE 2 Ingredients for Chemical Indicator Inks Ingredient Amount (g)Water 39.02 15% Polyvinyl alcohol 39.02 Thickeners 7.57 Hexahydratemetal salt 7.28 Citric acid 3.989 pH indicators 1.04 Methyl cellulose1.03 Foam suppressor 0.033

Portions of the resulting chemical indicator inks were tested byexposure to ethylene oxide vapor in the presence of low-temperaturesteam for 4 hours at 125° F. (see Table 1 above). The gas concentrationwas 600 mg/l of ethylene oxide and nitrogen. Further portions of thechemical indicator inks were subjected to: 1) steam autoclavesterilization in the absence of ethylene oxide for 20 minutes at 250°F.; 2) dry heat for 30 minutes at 284° F.; and 3) steam formaldehydesterilization. These different sterilization processes resulted ineither no color change or a different color change than was obtainedfrom exposure to ethylene oxide. The results of these differentsterilization methods are shown in Table 3 below.

TABLE 3 pH Indicator Dye(s) Before and After Exposure to DifferentSterilization Methods Dry Heat Steam pH Indicator Original Steriliz-Steriliz- Formaldehyde No. Dye(s) Color ation ation Sterilization 1Bromocresol Brick red No color No color No color green + change changechange Methyl red 2 Bromophen- Orange Dark Green No color ol orange +green change Ethyl orange 3 Ethyl orange Pink Brown Dark pink Brown 4Bromophen- Yellow Dark No color No color ol blue green green changechange 5 Bromophen- Brick red No color Pink red No color ol blue +change change Methyl red 6 Bromocresol Orange Orange No color No colorgreen green change change

While certain representative embodiments and details have been shown forpurposes of illustrating the invention, it will be apparent to thoseskilled in the art that various changes in the compositions and methodsdisclosed herein may be made without departing from the scope of theinvention, which is defined in the appended claims.

1. A method for indicating that an article has undergone ethylene oxidesterilization processing comprising: providing a water-based chemicalindicator ink consisting essentially of at least one pH indicator dyeselected from the group consisting of Bromocresol green, Bromophenolblue, Methyl red, Ethyl orange, and combinations thereof, and a powderedand crystallized hexahydrate metal salt; wherein said at least one pHindicator dye undergoes an irreversible color change when exposed toethylene oxide vapor in the presence of low-temperature steam; applyingsaid water-based chemical indicator ink to an article; subjecting saidarticle to a concentration of ethylene oxide vapor in the presence oflow-temperature steam; and observing said water-based chemical indicatorink for a color change that is visually indicative of whether saidconcentration of ethylene oxide vapor has been applied for a timesufficient to sterilize said article.
 2. The method of claim 1 furthercomprising measuring the integrated effect of subjecting said article tosaid concentration of ethylene oxide vapor in the presence oflow-temperature steam for said time sufficient to sterilize saidarticle.
 3. The method of claim 1 wherein applying said water-basedchemical indicator ink to said article comprises applying saidwater-based chemical indicator ink to a substrate to form an ethyleneoxide sterilization process indicator and applying said ethylene oxidesterilization process indicator to said article.
 4. The method of claim3 further comprising printing said water-based chemical indicator ink onsaid substrate in the shape of squares or insignia to form said ethyleneoxide sterilization process indicator.
 5. The method of claim 3 furthercomprising securing said ethylene oxide sterilization process indicatorto a package containing said article and subjecting said package to saidconcentration of ethylene oxide vapor in the presence of low-temperaturesteam.
 6. The method of claim 1 wherein said at least one pH indicatordye does not undergo a color change when exposed to formaldehyde gas,high-temperature steam, dry heat, or combinations thereof.
 7. The methodof claim 1 wherein said at least one pH indicator dye undergoes a colorchange when exposed to formaldehyde gas, high-temperature steam, dryheat, or combinations thereof, that is different than is obtained whenexposed to ethylene oxide vapor.
 8. The method of claim 1 wherein saidwater-based chemical indicator ink further consists essentially of anacidic compound, wherein said acidic compound retards a color change ofsaid water-based chemical indicator ink.
 9. The method of claim 8wherein said acidic compound is citric acid.
 10. The method of claim 1wherein said water-based chemical indicator ink further consistingessentially of at least one thickening agent.
 11. The method of claim 10wherein said at least one thickening agent is selected from the groupconsisting of hydrous aluminum silicates, hydrous magnesium silicates,and combinations thereof.
 12. The method of claim 1 wherein saidwater-based chemical indicator ink further consists essentially of awhite pigment.
 13. The method of claim 12 wherein said white pigment istitanium dioxide.
 14. The method of claim 1 wherein said water-basedchemical indicator ink further consists essentially of a binder.
 15. Themethod of claim 14 wherein said binder is a polymeric material.
 16. Themethod of claim 15 wherein said polymeric material is selected from thegroup consisting of polyvinyl alcohol, methyl cellulose, andcombinations thereof.
 17. The method of claim 1 wherein said water-basedchemical indicator ink further consists essentially of a foamsuppressor.
 18. The method of claim 17 wherein said foam suppressor isan aliphatic polyol blend.
 19. A method for indicating that an articlehas undergone ethylene oxide sterilization processing comprising:providing a water-based chemical indicator ink consisting essentially ofa combination pH indicator dye selected from the group consisting ofBromophenol blue and Ethyl orange, Bromophenol blue and Methyl red,Bromocresol green and Ethyl orange, Bromocresol green and Bromophenolblue, and Methyl red and Ethyl orange, wherein said combination pHindicator dye undergoes an irreversible color change when exposed toethylene oxide vapor in the presence of low-temperature steam; applyingsaid water-based chemical indicator ink to an article; subjecting saidarticle to a concentration of ethylene oxide vapor in the presence oflow-temperature steam; and observing said water-based chemical indicatorink for a color change that is visually indicative of whether saidconcentration of ethylene oxide vapor has been applied for a timesufficient to sterilize said article.
 20. A method for indicating thatan article has undergone ethylene oxide sterilization processingcomprising: providing a water-based chemical indicator ink consistingessentially of a combination pH indicator dye selected from the groupconsisting of Bromophenol blue and Ethyl orange, Bromophenol blue andMethyl red, Bromocresol green and Ethyl orange, Bromocresol green andMethyl red, Bromocresol green and Bromophenol blue, and Methyl red andEthyl orange, wherein said combination pH indicator dye undergoes anirreversible color change when exposed to ethylene oxide vapor in thepresence of low-temperature steam wherein said water-based chemicalindicator ink is an aqueous ink solution; applying said water-basedchemical indicator ink to an article; subjecting said article to aconcentration of ethylene oxide vapor in the presence of low-temperaturesteam; and observing said water-based chemical indicator ink for a colorchange that is visually indicative of whether said concentration ofethylene oxide vapor has been applied for a time sufficient to sterilizesaid article.